During the past year, we have discovered a novel post-translational modification of PLA2 by transglutaminase (TG) which dramatically increases phospholipase A2 (PLA2) activity. TG-catalyzed incorporation of polyamine substrates of TG into PLA2 also significantly increases PLA2 activity. This post-translational modification leads to dimerization of PLA2 which is essential for the activation of this enzyme. Whether this form of post-translational modification of PLA2 plays a role in the activation of this enzyme, found in juvenile rheumatoid arthritis (JRA) and rheumatoid arthritis (RA), is now being investigated. The results of a follow up study on the mechanism of inhibition of PLA2 activity by uteroglobin (UG) and antiflammin peptides suggest that these inhibitors directly interact with PLA2 and inhibits the activation of this enzyme, possibly by interfering with the dimerization process. Using an animal model of human anterior uveitis we have demonstrated that topical application of antiflammin peptides is just as effective as corticosteroid therapy for this disease and are seemingly devoid of the side effects of steroid treatment. A collaborative clinical trial of these peptides on human anterior uveitis is now being implemented. In a separate study, we developed a monospecific neutralizing PLA2 antibody which dramatically inhibits the activity of this enzyme. Purified IgG, Fab2 and Fab1 molecules are equally effective as PLA2 inhibitors. Development of specific PLA2 inhibitory oligopeptides on the basis of this antibody structure is now underway. A cDNA coding for the human UG-like protein has been obtained and now being expressed in E. coli using an expression vector pLE 103-1 which we developed in our laboratory. Characterization and site-directed mutagenesis studies are conducted to determine the structure-function relationship of this protein. In a separate study, we compared the pattern of arachidonate release in bradykinin (BDK)-stimulated fibroblasts from Cystic Fibrosis (CF) patients and those obtained from healthy individuals. We found that although there is no difference in the basal level of arachidonate release between normal and CF cells there is a significant difference among these cells after stimulation with BDK. The relationship between CFTR mutation and abnormal arachidonate release as they relate to chloride channel abnormality in CF is now being investigated.